[Federal Register: September 13, 2004 (Volume 69, Number 176)]
[Notices]               
[Page 55164-55165]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr13se04-49]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D-0378]

 
International Conference on Harmonisation; Draft Guidance on S7B 
Nonclinical Evaluation of the Potential for Delayed Ventricular 
Repolarization (QT Interval Prolongation) by Human Pharmaceuticals; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a revised draft guidance entitled ``S7B Nonclinical 
Evaluation of the Potential for Delayed Ventricular Repolarization (QT 
Interval Prolongation) by Human Pharmaceuticals.'' The draft guidance 
was prepared under the auspices of the International Conference on 
Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH). The draft guidance describes a 
nonclinical testing strategy for assessing the potential of a test 
substance to delay ventricular repolarization and includes information 
concerning nonclinical assays and an integrated risk assessment. The 
draft guidance is intended to facilitate the nonclinical assessment of 
the effects of pharmaceuticals on ventricular repolarization and 
proarrhythmic risk.

DATES: Submit written or electronic comments on the draft guidance by 
December 13, 2004.

ADDRESSES: Submit written comments on the draft guidance to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic 
comments to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. Submit written 

requests for single copies of the draft guidance to the Division of 
Drug Information (HFD-240), Center for Drug Evaluation and Research, 
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857; 
or the Office of Communication, Training and Manufacturers Assistance 
(HFM-40), Center for Biologics Evaluation and

[[Page 55165]]

Research (CBER), Food and Drug Administration, 1401 Rockville Pike, 
Rockville, MD 20852-1448. The guidance may also be obtained by mail by 
calling the CBER Voice Information System at 1-800-835-4709 or 301-827-
1800. Send two self-addressed adhesive labels to assist the office in 
processing your requests. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the revised draft guidance document.

FOR FURTHER INFORMATION CONTACT: 
    Regarding the guidance: John Koerner, Center for Drug Evaluation 
and Research (HFD-110), Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857, 301-594-5338.
    Regarding the ICH: Michelle Limoli, Office of International 
Programs (HFG-1), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-4480.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for drug development among regulatory agencies.
    ICH was organized to provide an opportunity for tripartite 
harmonization initiatives to be developed with input from both 
regulatory and industry representatives. FDA also seeks input from 
consumer representatives and others. ICH is concerned with 
harmonization of technical requirements for the registration of 
pharmaceutical products among three regions: The European Union, Japan, 
and the United States. The six ICH sponsors are the European 
Commission; the European Federation of Pharmaceutical Industries 
Associations; the Japanese Ministry of Health and Welfare; the Japanese 
Pharmaceutical Manufacturers Association; the Centers for Drug 
Evaluation and Research and Biologics Evaluation and Research, FDA; and 
the Pharmaceutical Research and Manufacturers of America. The ICH 
Secretariat, which coordinates the preparation of documentation, is 
provided by the International Federation of Pharmaceutical 
Manufacturers Associations (IFPMA).
    The ICH Steering Committee includes representatives from each of 
the ICH sponsors and the IFPMA, as well as observers from the World 
Health Organization, Health Canada, and the European Free Trade Area.
    In the Federal Register of June 14, 2002 (67 FR 40950), the agency 
made available a draft guidance entitled ``S7B Safety Pharmacology 
Studies for Assessing the Potential for Delayed Ventricular 
Repolarization (QT Interval Prolongation) by Human Pharmaceuticals'' 
and invited public comment. After considering the comments, the Safety 
Expert Working Group of the ICH made extensive changes to the document, 
including changes to the title of the draft guidance, the testing 
strategy, and the timing of nonclinical studies relative to clinical 
development.
    In June 2004, the ICH Steering Committee agreed that a revised 
draft guidance entitled ``S7B Nonclinical Evaluation of the Potential 
for Delayed Ventricular Repolarization (QT Interval Prolongation) by 
Human Pharmaceuticals'' should be made available for public comment. 
Comments about this draft will be considered by FDA and the Safety 
Expert Working Group.
    The draft guidance provides guidance on nonclinical assessment of 
the effects of pharmaceuticals on ventricular repolarization and 
proarrhythmic risk. The draft guidance describes a nonclinical testing 
strategy for assessing the potential of a test substance to delay 
ventricular repolarization and includes information concerning 
nonclinical assays and an integrated risk assessment.
    This draft guidance, when finalized, will represent the agency's 
current thinking on this topic. It does not create or confer any rights 
for or on any person and does not operate to bind FDA or the public. An 
alternative approach may be used if such approach satisfies the 
requirements of the applicable statutes and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments on the draft guidance. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. The draft guidance and received 
comments may be seen in the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm, or http://www.fda.gov/cber/publications.htm.


    Dated: September 3, 2004.
William K. Hubbard,
Associate Commissioner for Policy and Planning.
[FR Doc. 04-20564 Filed 9-10-04; 8:45 am]

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